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Cloning and stem cell Nobel for Gurdon and Yamanaka

By Andy Coghlan

This year’s Nobel prize in Physiology or Medicine has been awarded to John Gurdon at the University of Cambridge and Shinya Yamanaka, who splits his time between Kyoto University in Japan and the Gladstone Institutes in San Francisco. They rewrote biology textbooks by showing that mature cells could be reprogrammed into embryonic cells that could then turn into all other tissues of the body.

In 1962, Gurdon showed that frog eggs grew into healthy tadpoles even though he had removed the original nucleus and replaced it with the nucleus from a gut cell taken from a mature frog.

Then in 2006, Yamanaka showed that by inserting just four “rejuvenation” genes into skin cells, he could rewind their genetic code, turning them back into embryo-like cells that he called induced pluripotent stem (iPS) cells.

“If it really works, it would be remarkable and immensely useful, both scientifically and therapeutically,” Gurdon told New Scientist at the time of Yamanaka’s discovery. “It’s surprising to me that it works, and I’m sure there will be lots of labs trying to repeat and refine it.”

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Both breakthroughs destroyed the long-held dogma that once cells had matured into specific tissue types, such as skin, brain or muscle, they could never regress back to the state from which they originated in an embryo.

“This joint Nobel Prize traces and celebrates the wonderful scientific journey from John Gurdon’s pioneering early work to the sensational discovery of somatic cell reprogramming by Shinya Yamanaka,” said Anthony Hollander, head of cellular and molecular medicine at the University of Bristol, UK. “It’s fantastic news for stem-cell research and for UK science.”

Double vision

Back in the 1960s, Gurdon also showed that tadpoles could be cloned into healthy frogs. This was the prelude to the creation of Dolly the sheep, the first mammal produced from a single mature cell. Dolly was created by rewinding an udder cell into an embryonic state, then fusing its DNA with an egg cell that had been stripped of its nucleus.

Yamanaka’s breakthrough in 2006 raised the prospect of growing tissues from a person’s own cells. Skin cells, for example, could be taken from a patient, rewound to an embryonic state, then turned into whatever tissue was needed.

Researchers had already shown that they could do this using pluripotent cells from human embryos, called human embryonic stem cells. But because human embryos had to be destroyed to obtain the cells, the technique was widely opposed by anti-abortion groups, especially in the US.

Yamanaka’s technique overcame this objection, raising the prospect of producing tissues without the need to destroy embryos.

Safety first

Nobody has yet been treated with iPS cells as there are still safety issues to be resolved. For example, Yamanaka inserted his rejuvenation genes into mature cells with the help of a virus, a process that could also lead to cancer-causing oncogenes being activated.

Furthermore, researchers showed last year that mice that received iPS cells displayed an immune response even though the cells were made from their own tissue. That suggests there is something in these cells that makes them different from native tissue, and therefore potentially harmful.